PROJECT SUMMARY/ABSTRACT Chronic hepatitis C virus (HCV) affects approximately 3.5 million individuals in the United States. Given the primary mode of transmission is through infected needles, the ongoing nationwide opioid epidemic will continue to result in an increase in new cases. Direct-acting antiviral (DAA) medications, introduced in November 2013 and later, are significantly more effective in treating HCV with fewer side effects but also more expensive than older interferon-based regimens. Early evidence suggests, however, that these medications have not been rapidly adopted throughout the healthcare system. Due to high cost, some payers initially declined coverage or enacted prior authorization (PA) restrictions to limit treatment to patients with advanced disease or no active substance use disorder (SUD), or required specific prescribing provider specialties. PA restrictions, however, are not the only barrier to patients receiving treatment. We conducted an analysis of sofosbuvir and simeprevir uptake, DAA medications introduced in late 2013, in the Massachusetts Medicaid program, a program that did not restrict reimbursement based on any of these criteria. Despite less restrictive policies, uptake was low (5%) during the first eight months of their availability. Patient and provider factors associated with treatment were identified. These results suggest that diffusion of new DAA medications in a Medicaid population is complex, with patient barriers to care, provider prioritization, provider knowledge, and organizational factors all potentially playing a role in determining which patients receive treatment. Using a diffusion of innovation framework, the proposed project will use a mixed methods approach, including claims analysis and case studies, to expand upon the initial Massachusetts findings to examine uptake of newer DAA regimens across multiple states. We will perform multi-state Medicaid claims analyses to: examine trends in uptake of new DAA medications in the Medicaid population (Specific Aim 1); and identify patient, provider, and contextual factors that predict treatment (Specific Aim 2). In addition, we will conduct key informant interviews to provide insight into how and why key determinants are associated with higher rates of eligible patients getting treatment (Specific Aim 3). The central hypothesis underlying our project is that multiple factors, including, patient, provider and policy-level factors all affect diffusion of these new medications. The project will help Medicaid agencies and health care practices translate evidence-based care into clinical practice. Findings will provide insight as to how providers choose candidates for treatment and will identify patient or provider groups who may benefit from outreach to improve access. Results may help payers and providers identify opportunities to enhance care coordination and improve patient outcomes. Finally, the project will provide an example of uptake of a breakthrough therapy in Medicaid populations, which may assist state Medicaid agencies, other payers, and providers in planning for the introduction of future medications.